RESTORING NORMAL FREQUENCY AND DURATION OF FEMALE SEXUAL BEHAVIOR

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目的：提高对绒猴雌猴性反应调节的神经机制的认识，为临床干预女性性功能减退提供依据。 据估计，性功能障碍影响了43%的女性。目前还没有批准的药物治疗这种疾病。对雌激素和孕激素激素治疗的安全性担忧促使人们寻求非甾体药物治疗。5-羟色胺（5-HT）神经元系统参与调节一系列雌性哺乳动物的性行为，包括人类和非人类灵长类动物，但所涉及的机制还不清楚。我们开发了一个模型系统与女性普通绒猴证明，flibanserin刺激5-HT 1A（激动剂）和5-HT 2A（拮抗剂）突触后受体增加男性注意女性生殖器区域，而不改变女性的性行为，而慢性刺激前和突触后5-HT 1A受体8-OH-DPAT减少女性性接受性。氟班色林还鼓励治疗的女性和他们的男性伴侣之间的积极动态（allogrooming），与8-OH-DPAT（侵略，男性的性排斥）的负面动态。氟班色林的突触后作用可能优先集中在前额叶皮层。由于接受雌二醇或不接受激素的女性之间没有观察到行为差异，氟班色林可能通过支持与伴侣的积极互动来抵消绝经前后女性的性欲低下。 本研究使用WNPRC Assay Services和Animal Services。 出版物待定。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To improve our understanding of serotonin-related neural mechanisms regulating female sexual response in marmosets in order to develop more appropriate clinical intervention for sexual hypofunction in women. Sexual dysfunction affects an estimated 43% of women. Currently there are no approved drug therapies for this disorder. Safety concerns about hormonal treatment with estrogens and progestogens motivates the search for non-steroidal pharmoacotherapy. The serotonin (5-HT) neuronal system has been implicated in regulating sexual behavior in a range of female mammals, including humans and nonhuman primates, but the mechanisms involved are not well understood. We developed a model system with female common marmosets to demonstrate that flibanserin stimulation of 5-HT1A (agonist) and 5-HT2A (antagonist) postsynaptic receptors increases male attention to female genital area without altering female sexual behavior, while chronic stimulation of pre- and post-synpatic 5-HT1A receptors by 8-OH-DPAT diminishes female sexual receptivity. Flibanserin also encourages a positive dynamic (allogrooming) between treated females and their male pairmates, in contrast to the negative dynamic engaged by 8-OH-DPAT (aggression, sexual rejection of the male). Postsynaptic action of flibanserin may be preferentially focused on the prefrontal cortex. As there were no observed behavioral differences between females receiving estradiol or no hormone, flibanserin may counteract low sexual desire in women, before or after menopause, by supporting positive interactions with their partner. This research used WNPRC Assay Services and Animal Services. Publications are pending.